Epigenetic modifiers as new immunomodulatory therapies in solid tumours

INTERIM REPORT FROM A PHASE 2 MULTICENTER STUDY OF TAZEMETOSTAT, AN EZH2 INHIBITOR, IN PATIENTS WITH RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMAS

(2017) F. Morschhauser et al.   HEMATOLOGICAL ONCOLOGY

Polycomb Repressive Complex 2-Mediated Chromatin Repression Guides Effector CD8 + T Cell Terminal Differentiation and Loss of Multipotency

(2017) Simon M. Gray et al.   IMMUNITY

SATB1 Expression Governs Epigenetic Repression of PD-1 in Tumor-Reactive T Cells

(2017) Tom L. Stephen et al.   IMMUNITY

Metabolic and Epigenetic Coordination of T Cell and Macrophage Immunity

(2017) Anthony T. Phan et al.   IMMUNITY

The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression

(2017) Wen Pan et al.   IMMUNITY

Anti-Inflammatory Chromatinscape Suggests Alternative Mechanisms of Glucocorticoid Receptor Action

(2017) Kyu-Seon Oh et al.   IMMUNITY

DNA methylation–based immune response signature improves patient diagnosis in multiple cancers

(2017) Jana Jeschke et al.   JOURNAL OF CLINICAL INVESTIGATION

The chromatin accessibility signature of human immune aging stems from CD8+T cells

(2017) Duygu Ucar et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis

(2017) Hossam A. Abdelsamed et al.   JOURNAL OF EXPERIMENTAL MEDICINE

HEXIM1 and NEAT1 Long Non-coding RNA Form a Multi-subunit Complex that Regulates DNA-Mediated Innate Immune Response

(2017) Mehdi Morchikh et al.   MOLECULAR CELL

CDK4/6 inhibition triggers anti-tumour immunity

(2017) Shom Goel et al.   NATURE

Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages

(2017) Jennifer L. Guerriero et al.   NATURE

Identification of essential genes for cancer immunotherapy

(2017) Shashank J. Patel et al.   NATURE

Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming

(2017) Lin Tian et al.   NATURE

Tumour-associated macrophages as treatment targets in oncology

(2017) Alberto Mantovani et al.   Nature Reviews Clinical Oncology

Selective inhibition of BET proteins reduces pancreatic damage and systemic inflammation in bile acid- and fatty acid ethyl ester- but not caerulein-induced acute pancreatitis

(2017) Wei Huang et al.   PANCREATOLOGY

Brd4 modulates the innate immune response through Mnk2–eIF4E pathway-dependent translational control of IκBα

(2017) Yan Bao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

(2017) Dung T. Le et al.   SCIENCE

Epigenetic plasticity and the hallmarks of cancer

(2017) William A. Flavahan et al.   SCIENCE

The cancer epigenome: Concepts, challenges, and therapeutic opportunities

(2017) Mark A. Dawson   SCIENCE

Combined antiangiogenic and anti–PD-L1 therapy stimulates tumor immunity through HEV formation

(2017) Elizabeth Allen et al.   Science Translational Medicine

BET bromodomain inhibitors synergize with ATR inhibitors in melanoma in melanoma

(2017) Somsundar Veppil Muralidharan et al.   Cell Death & Disease

Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non–Small Cell Lung Cancer

(2017) Dennis O. Adeegbe et al.   Cancer Discovery

Chromatin state dynamics during NK cell activation

(2017) Yang Li et al.   Oncotarget

BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1

(2017) Simon J. Hogg et al.   Cell Reports

Glioma-induced SIRT1-dependent activation of hMOF histone H4 lysine 16 acetyltransferase in microglia promotes a tumor supporting phenotype

(2017) Dalel Saidi et al.   OncoImmunology

Suppression of indoleamine-2,3-dioxygenase 1 expression by promoter hypermethylation in ER-positive breast cancer

(2017) Dyah L. Dewi et al.   OncoImmunology

Bromodomain and Extra-Terminal Protein Inhibition Attenuates Neutrophil-dominant Allergic Airway Disease

(2017) Michelle L. Manni et al.   Scientific Reports

Combining Epigenetic and Immunotherapy to Combat Cancer

(2016) Katherine B. Chiappinelli et al.   CANCER RESEARCH

Window of opportunity studies: Do they fulfil our expectations?

(2016) Sandra Schmitz et al.   CANCER TREATMENT REVIEWS

Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma

(2016) Willy Hugo et al.   CELL

Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1

(2016) Stéphane Champiat et al.   CLINICAL CANCER RESEARCH

Innovations for phase I dose-finding designs in pediatric oncology clinical trials

(2016) Adelaide Doussau et al.   Contemporary Clinical Trials

Epigenomic Profiling of Human CD4 + T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

(2016) Pawel Durek et al.   IMMUNITY

BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models

(2016) Yuki Kagoya et al.   JOURNAL OF CLINICAL INVESTIGATION

HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues

(2016) Xiaoyu Lin et al.   MOLECULAR CANCER THERAPEUTICS

BET bromodomain inhibition reduces maturation and enhances tolerogenic properties of human and mouse dendritic cells

(2016) Ronald Schilderink et al.   MOLECULAR IMMUNOLOGY

Ionic immune suppression within the tumour microenvironment limits T cell effector function

(2016) Robert Eil et al.   NATURE

Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment

(2016) Yohko Kitagawa et al.   NATURE IMMUNOLOGY

Targeting the cancer epigenome for therapy

(2016) Peter A. Jones et al.   NATURE REVIEWS GENETICS

The molecular hallmarks of epigenetic control

(2016) C. David Allis et al.   NATURE REVIEWS GENETICS

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck

(2016) Robert L. Ferris et al.   NEW ENGLAND JOURNAL OF MEDICINE

The epigenetic landscape of T cell exhaustion

(2016) D. R. Sen et al.   SCIENCE

Trained immunity: A program of innate immune memory in health and disease

(2016) M. G. Netea et al.   SCIENCE

Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade

(2016) P.-L. Chen et al.   Cancer Discovery

Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628

(2016) A. Stathis et al.   Cancer Discovery

BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression

(2016) Hengrui Zhu et al.   Cell Reports

Distinct Trends of DNA Methylation Patterning in the Innate and Adaptive Immune Systems

(2016) Ronald P. Schuyler et al.   Cell Reports

Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells

(2016) Amelia J. Tesone et al.   Cell Reports

The interplay of epigenetic therapy and immunity in locally recurrent or metastatic estrogen receptor-positive breast cancer: Correlative analysis of ENCORE 301, a randomized, placebo-controlled phase II trial of exemestane with or without entinostat

(2016) Yusuke Tomita et al.   OncoImmunology

A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC

(2015) Helai P. Mohammad et al.   CANCER CELL

PRC2 Epigenetically Silences Th1-Type Chemokines to Suppress Effector T-Cell Trafficking in Colon Cancer

(2015) Nisha Nagarsheth et al.   CANCER RESEARCH

TET2 Mutations Affect Non-CpG Island DNA Methylation at Enhancers and Transcription Factor-Binding Sites in Chronic Myelomonocytic Leukemia

(2015) J. Yamazaki et al.   CANCER RESEARCH

DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts

(2015) David Roulois et al.   CELL

Molecular Pathways: At the Crossroads of Cancer Epigenetics and Immunotherapy

(2015) M. Maio et al.   CLINICAL CANCER RESEARCH

302 A phase 1 study of EPZ-6438 (E7438), an Enhancer of Zeste-Homolog 2 (EZH2) inhibitor: Preliminary activity in INI1-negative tumors

(2015) A. Italiano et al.   EUROPEAN JOURNAL OF CANCER

The Chromatin-Modifying Enzyme Ezh2 Is Critical for the Maintenance of Regulatory T Cell Identity after Activation

(2015) Michel DuPage et al.   IMMUNITY

Immunity, inflammation, and cancer: an eternal fight between good and evil

(2015) Shabnam Shalapour et al.   JOURNAL OF CLINICAL INVESTIGATION

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

(2015) Robert J. Motzer et al.   JOURNAL OF CLINICAL ONCOLOGY

Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy

(2015) Dongjun Peng et al.   NATURE

New IDH1 mutant inhibitors for treatment of acute myeloid leukemia

(2015) Ujunwa C Okoye-Okafor et al.   Nature Chemical Biology

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

(2015) Dung T. Le et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pembrolizumab versus Ipilimumab in Advanced Melanoma

(2015) Caroline Robert et al.   NEW ENGLAND JOURNAL OF MEDICINE

Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

(2015) James Larkin et al.   NEW ENGLAND JOURNAL OF MEDICINE

Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity

(2015) Jie Yin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

T cell exclusion, immune privilege, and the tumor microenvironment

(2015) J. A. Joyce et al.   SCIENCE

Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer

(2015) N. A. Rizvi et al.   SCIENCE

Manipulation of B-cell responses with histone deacetylase inhibitors

(2015) Michaela Waibel et al.   Nature Communications

Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma

(2015) Tim Hensel et al.   Oncotarget

EZH2 is crucial for both differentiation of regulatory T cells and T effector cell expansion

(2015) Xiang-Ping Yang et al.   Scientific Reports

Alterations of immune response of non-small cell lung cancer with Azacytidine

(2015) John Wrangle et al.   Oncotarget

Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers

(2015) Huili Li et al.   Oncotarget

The Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition

(2014) Junwei Shi et al.   MOLECULAR CELL

Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer

(2014) Irfan A. Asangani et al.   NATURE

Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients

(2014) Roy S. Herbst et al.   NATURE

PD-1 blockade induces responses by inhibiting adaptive immune resistance

(2014) Paul C. Tumeh et al.   NATURE

Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma

(2014) Alexandra Snyder et al.   NEW ENGLAND JOURNAL OF MEDICINE

Erasers of Histone Acetylation: The Histone Deacetylase Enzymes

(2014) E. Seto et al.   Cold Spring Harbor Perspectives in Biology

An Intact Immune System Is Required for the Anticancer Activities of Histone Deacetylase Inhibitors

(2013) A. C. West et al.   CANCER RESEARCH

A comparative analysis of paediatric dose-finding trials of molecularly targeted agent with adults’ trials

(2013) Xavier Paoletti et al.   EUROPEAN JOURNAL OF CANCER

The Polycomb Protein Ezh2 Regulates Differentiation and Plasticity of CD4+ T Helper Type 1 and Type 2 Cells

(2013) Damon J. Tumes et al.   IMMUNITY

Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer

(2013) Christoph Plass et al.   NATURE REVIEWS GENETICS

Analysis of the levels of lysine-specific demethylase 1 (LSD1) mRNA in human ovarian tumors and the effects of chemical LSD1 inhibitors in ovarian cancer cell lines

(2013) Sergiy Konovalov et al.   Journal of Ovarian Research

Immunogenic Cell Death in Cancer Therapy

(2012) Guido Kroemer et al.   Annual Review of Immunology

Lysine-specific demethylase 1 (LSD1) and histone deacetylase 1 (HDAC1) synergistically repress proinflammatory cytokines and classical complement pathway components

(2012) Andreas Janzer et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

The bromodomain interaction module

(2012) Panagis Filippakopoulos et al.   FEBS LETTERS

IDH mutation impairs histone demethylation and results in a block to cell differentiation

(2012) Chao Lu et al.   NATURE

IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype

(2012) Sevin Turcan et al.   NATURE

An epigenetic silencing pathway controlling T helper 2 cell lineage commitment

(2012) Rhys S. Allan et al.   NATURE

The combination of histone deacetylase inhibitors with immune-stimulating antibodies has potent anti-cancer effects

(2012) Alison C. West et al.   OncoImmunology

Early epigenetic events regulate the adaptive immune response gene CIITA

(2011) Ninad T. Mehta et al.   Epigenetics

The Polycomb complex PRC2 and its mark in life

(2011) Raphaël Margueron et al.   NATURE

Eradication of solid tumors using histone deacetylase inhibitors combined with immune-stimulating antibodies

(2011) A. J. Christiansen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non-Small Cell Lung Cancer

(2011) R. A. Juergens et al.   Cancer Discovery

Reversal of Histone Methylation: Biochemical and Molecular Mechanisms of Histone Demethylases

(2010) Nima Mosammaparast et al.   Annual Review of Biochemistry

Suppression of inflammation by a synthetic histone mimic

(2010) Edwige Nicodeme et al.   NATURE